食管癌组织中金属硫蛋白3基因甲基化的地区性差异

目的:探讨食管癌高发区河北省中南部及广东省潮汕地区和食管癌非高发区的食管癌及正常组织中金属硫蛋白3 (metallothionein-3, MT-3)基因CpG岛的甲基化情况及其临床意义.方法:选取正常人血液标本10例,胎儿食管组织标本10例,非食管癌高发区正常人食管黏膜标本20例,河北省中南部食管癌高发区和潮汕地区食管癌新鲜手术标本及切缘正常组织各30例;应用甲基化特异性聚合酶链反应 (methylation-specific PCR, MSP)检测其MT-3基因CpG岛的甲基化情况,并分析其与临床病理资料之间的关系.结果: 高发区食管癌患者的切缘正常组织有20例(33.3%)存在MT-3基因甲基化,高于非高发区正常人食管黏膜(P=0.013);食管癌组织中有49例(81.7%)甲基化,明显高于相应肿瘤切缘正常组织(P<0.001),但2个高发区之间比较差异无统计学意义(P=0.739).结论:食管癌患者的正常食管黏膜及癌组织中均广泛存在MT-3基因的甲基化,后天因素刺激可能是导致MT-3基因甲基化的重要原因.

Regional differences of methylation of metallothionein-3 gene in tissues of esophageal cancer

Objective:To investigate the methylation of CpG island of metallothionein-3 (MT-3) gene in esophageal cancer tissues and normal tissues in middle and south area of Hebei Province and Chaoshan area of Guangdong Province and compared the results with those in low risk area of esophageal cancer. Methods:The blood samples from 10 normal volunteers, 10 embryonic esophageal tissues, 20 esophageal mucosa tissues from normal subjects in low risk area as well as 30 fresh surgical specimens of esophageal cancer and 30 normal marginal tissues in the high risk middle-south Hebei Province and Chaoshan area were collected. Methylation-specific polymerase chain reaction (MSP) was used to detect the methylation status of the CpG island of MT-3 gene in these samples. Its relationship with clinicopatho-logical features was analyzed. Results:There were 20 (33.3%) cases with MT-3 methylation in the marginal tissues of esophageal cancer from high-risk area, which was higher than that in the normal mucosa from low-risk area (P=0.013). And there were 49 (81.7%) cases with MT-3 methylation in esophageal cancer tissues, which was higher than that in normal marginal tissues (P<0.001). But there was no significant difference in the methylation degree between middle-south of Hebei Province and Chaoshan area (P=0.739). Conclusion:MT-3 methylation widely exists in esophageal mucosa and carcinoma tissues. Acquired stimulus may be the main cause of these methylations.